ABSTRACT:
Personalized approaches to pharmacotherapy are an important direction of modern medicine, ensuring the individualization of dosing, increased treatment effectiveness, and patient safety. In the absence of industrial pediatric dosage forms of medicinal products, extemporaneous compounding is a relevant solution, which at the same time requires reliable methods of quality control and confirmation of stability. Special attention should be paid to medicinal products that are used off-label in young children, in particular propranolol hydrochloride — a ß-adrenoblocker approved by the FDA as a first-line agent for the treatment of infantile hemangioma. At the same time, pediatric dosage forms of propranolol are absent on the pharmaceutical market of Ukraine, and the use of preservatives such as sodium benzoate or methylparaben in infants is undesirable due to the risks of toxic effects. This necessitates the development of a safe composition and the assessment of the stability of the solution in the absence of preservatives. The aim of the study was the adaptation of a pharmacopoeial HPLC method for the quantitative determination of propranolol hydrochloride in order to evaluate the stability of the oral dosage form prepared in small batches under pharmacy manufacturing conditions. The study was carried out on samples of the medicinal product “Propranolol hydrochloride, 4.28 mg/mL, oral solution,” prepared by Pharmacy No. 2 ?hemoteka of the Pharmaceutical Department of JS? “Infuzia” (Ukraine). The proposed HPLC method based on the USP monograph “Propranolol Hydrochloride” is founded on the principles of international standards (USP, Ph. Eur., SphU, ICH Q2(R1)) and provides for the evaluation of such validation parameters as specificity, linearity, accuracy, precision, and solution stability. The obtained results confirmed that the method ensures clear separation of propranolol hydrochloride and excipients of the dosage form, is characterized by high reproducibility (r = 0.99997), accuracy (recovery 111.8–119.1%), and demonstrates the chemical stability of the studied medicinal product during 6 months of storage. The proposed adapted HPLC method can be implemented as a standard analytical tool for quality control and stability assessment of extemporaneous liquid dosage forms of propranolol used in pediatrics. The results of the study are of practical importance for pharmaceutical laboratories, pharmacy manufacturing facilities, and developers of pediatric dosage forms, contributing to improving the quality and safety of pharmaceutical care for the pediatric population.